This proposal is to request support for a Keystone Symposia meeting entitled NF-kappaB, organized by Vishva M. Dixit, Shao-Cong Sun and Sankar Ghosh, which will be held in Fairmont Banff Springs in Alberta, Canada from February 12-17, 2008. Research focused on NF-kappaB has continued to grow exponentially in recent years, fueled in part by the progress in accruing basic knowledge on this pathway, which in turn has provided the stimulus for applied research. Continued growth in this field is also the result of discoveries that reveal the ever-increasing importance of NF-kappaB in many cell types in both normal health and disease. NF-kappaB has become an integral part of diverse research disciplines, including immunology, signal transduction, chromatin regulation, autoimmune diseases, diabetes, osteoporosis and cancer, just to name a few. NF-kappaB is of great interest to clinical research and remains a prime target for therapeutic intervention in many diseases. The 2008 Keystone meeting on NF-kappaB will come at a particularly exciting time, when a number of unexpected new regulatory pathways and functions of this transcription factor family are emerging. For example extensive regulation of NF-kappaB at the chromatin level occurs in addition to the primary regulation, which is relief of inhibition by IkappaB proteins that normally keep NF-kappaB inactive in the cytoplasm. Regulation at the chromatin level is accomplished via signal-induced modifications of NF-kappaB itself or of interacting partners. An additional area of great activity has been the discovery of regulatory ubiquitination events in multiple steps of the NF-kappaB pathway, and we anticipate that the meeting will provide significant new insight in this area. In recent years evidence for the importance and extent of inappropriate activation of NF-kappaB in tumorigenesis has continued to emerge. The link between inflammation (via NF-kappaB) and tumorigenesis has led to tremendous interest in this area and we anticipate that significant new information will be presented at this meeting. New data will be presented on the roles of NF-kappaB in multiple myeloma, squamous head and neck cancers, breast cancer and diffuse large B cell lymphomas. Clinical trials are underway to evaluate NF-kappaB as a therapeutic target in these and other malignancies, and results from such trials are expected at this meeting. PROJECT NARRATIVE Research focused on NF-kappaB has continued to grow exponentially in recent years, and resultant discoveries reveal the ever-increasing importance of NF-kappaB in many cell types in both health and disease. NF-kappaB is of great interest to clinical research among diverse research disciplines such as immunology, signal transduction, and chromatin regulation; NF-kappaB is a prime target for therapeutic intervention in many diseases, including autoimmune diseases, diabetes, osteoporosis, and cancer.